By Amy Coopes (AFP) – Oct 31, 2010
SYDNEY:- Australian and British scientists have uncovered a "death" protein that destroys rogue cells in what could be breakthrough for the fight against cancer, malaria and diabetes, researchers said Monday.
The protein, perforin, targets wayward cells and punches a hole in their membranes to let in killer enzymes, project leader James Whisstock said, adding the discovery "answers a really fundamental mystery of immunity".
"Perforin is our body's weapon of cleansing and death," said Whisstock, from Australia's Monash University.
"It breaks into cells that have been hijacked by viruses or turned into cancer cells and allows toxic enzymes in, to destroy the cell from within," he said. "Without it, our immune system can't destroy these cells."
High-powered microscopes in Australia and at London's Birkbeck College had allowed scientists to examine perforin's structure and function, Whisstock said, revealing a "powerful molecule" that targets malignant or infected cells.
Without perforin -- released by "killer" cells designed to destroy harmful invaders -- the body was unable to fight infections. Studies with mice had linked defective perforin to leukaemia and heightened cell malignancy.
The discovery also had implications for autoimmune diseases such as juvenile type 1 diabetes and for transplant patients, with the protein linked to both the elimination of healthy cells and tissue rejection, added Whisstock.
"Now we know how it works, we can start to fine-tune it to fight cancer, malaria and diabetes," Whisstock said.
Fellow researcher Joe Trapani said the 10-year study found that perforin's structure was similar to bacterial toxins like anthrax and listeria, suggesting that the human body had learned its tactics from diseases themselves.
"Quite remarkably that mechanism is conserved all the way back to bacteria... we've actually pinched it off bacteria at some point (in human evolution) and turned it back against them," said Trapani, from Melbourne's Peter MacCallum Cancer Centre.
"It's a war conducted between our immune system and bacteria and we're actually fighting using similar weapons," he told AFP, explaining that it was two billion year old blueprint.
Trapani said the discovery had exciting and diverse applications ranging from "stuff in third-world countries with the malaria all the way through to more Western-style medicine with transplantation and so on."
Whisstock said researchers were looking for ways to inhibit and boost perforin and use it to "deliver toxic cargoes into cells by choice", hoping to pave the way for new drugs.
"I have worked on this for a long time and it answers a really fundamental mystery of immunity," Whisstock told ABC radio.
"So I think just from a fundamental science perspective, I think it is really, really important and it is actually also a really cool story."
